ENHANCED FRAGILITY OF NEURAL LYSOSOMES FROM CHICKS SUFFERING FROM GALACTOSE TOXICITY 1

—The stability of neural lysosomes to osmotic and temperature shock and the free (non‐sedimentable) activities of selected lysosomal hydrolases from chicks suffering from galactose neurotoxicity were investigated. The neural lysosomes from chicks fed galactose demonstrated enhanced fragility to both elevated temperature and hypo‐osmotic media in comparison to the behavior of neural lysosomes isolated from control animals. The increased lability to osmotic shock could be duplicated by preincubation of normal lysosomes in solutions of galactose or galactitol. Further, the increased fragility induced in vivo by galactose feeding could be reversed by removing the chicks from the diet for 8 h, and such removal was accompanied in the brain by large reductions in levels of galactose and galactitol. The free activities of both β‐galactosidase (EC 3.2.1.23) and β‐N‐acetyl hexosaminidase (EC 3.2.1.30) were elevated above those of controls, and the percentage increases were proportional to the combined brain levels of galactose and galactitol. Our data suggest that increased fragility of lysosomes is a function of the accumulation of galactose and galactitol in the brains of chicks fed toxic amounts of galactose. Alteration of lysosomal integrity represents an attractive role for galactitol, as well as galactose, in the causation of galactose neurotoxicity in chicks.